Renal Nerve Stimulation and Renal Denervation in Patients With Sympathetic Ventricular Arrhythmias

NCT02856373 | Terminated Phase 2

• 1 other identifier: 9218
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Sympathetic activity plays an important role in the pathogenesis of ventricular tachyarrhythmia. Previous studies have shown evidence of significant heritable influences on individual responses to adrenergic stimulation. Catheter-based renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce local and whole-body sympathetic activity. The investigators hypothesize that percutaneous transluminal electrical stimulation of the sympathetic nerve bundles in the renal arteries will cause ventricular arrhythmias and renal denervation will suppress these arrhythmias in patients with sympathetic ventricular arrhythmias. Objective: This study will investigate the effects of renal nerve stimulation before and after percutaneous transluminal RDN on cardiac excitable properties including induction of ventricular tachy-arrhythmias before and after RDN in six studies, i.e. patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome and arrhythmogenic right ventricular cardiomyopathy (ARVC), sympathetically driven ventricular arrhythmias, hypertrophic cardiomyopathy (HCM), dilated non-ischemic cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). The aim of the six studies is to assess the anti-arrhythmic effects of RDN in patients with sympathetic ventricular tachy-arrhythmias. Study design: Investigator initiated, multi centre, six pretest-posttest design studies. Study population: Patients with recurrent sympathetically driven ventricular arrhythmia despite optimal pharmacological therapy. Patients should be diagnosed with CPVT and certain types of long QT syndrome, ARVC, HCM, DCM and ICM. Eligible patients will be in the age category of 18-85 year. Intervention: RDN will be performed according to routine clinical practice. Prior to the ablation procedure, catheter mapping of the renal arteries will be performed according to routine clinical practice. Clinical and biological responses to transluminal electrical renal nerve stimulation will be assessed before and after RDN. Study endpoints:

• Main procedural study endpoint: Induction of ventricular arrhythmias in response to renal nerve stimulation prior to RDN and absence of renal nerves stimulation induced ventricular arrhythmias after RDN.
• Main clinical study endpoint: Development of ventricular arrhythmia during exercise stress testing performed 6 months after procedure. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In several studies, it was shown that RDN was safe. The intervention resulted in significantly better control of blood pressure with less medication, and beneficial changes in heart rate variability, autonomic sympathetic balance, renal arteriolar function, and a higher success of atrial fibrillation prevention. In case reports and case series, RDN had a favourable effect in patients with sympathetic drug refractory ventricular tachy-arrhythmias.

Conditions

Arrhythmias, Cardiac

Keywords

Denervation; Renal Artery

Outcome Measures

Primary Outcomes (2)

• Induction of ventricular arrhythmias (e.g. ventricular tachycardia and ventricular fibrillation)

  Induction of ventricular arrhythmias in response to RNS prior to RDN and absence of RNS induced ventricular arrhythmias after RDN

  A few minutes before RDN RNS will be performed. Time frame before RDN: 0-10 min. after RNS and before RDN. Time frame after RDN: 0-10 min.

• Development of ventricular arrhythmia

  Development of ventricular arrhythmia during exercise stress testing performed 6 months after procedure/intervention

  6 months after procedure/intervention

Secondary Outcomes (14)

• Time to first detection of ventricular arrhythmia or appropriate ICD therapy

  procedure/intervention-12 month follow up

• Changes in ventricular refractoriness (frequency)

  procedure/intervention

• Changes in ventricular refractoriness (duration)

  procedure/intervention

• Number of ventricular arrhythmias

  procedure/intervention

• Ventricular arrhythmia burden

  procedure/intervention- 6,12 months follow up

Study Arms (6)

CPVT

OTHER

catecholaminergic polymorphic ventricular tachycardia (CPVT) patients

Procedure: RNS and RDN

long QT syndrome

OTHER

long QT syndrome patients

Procedure: RNS and RDN

ARVC

OTHER

arrhythmogenic right ventricular cardiomyopathy (ARVC) patients

Procedure: RNS and RDN

HCM

OTHER

hypertrophic cardiomyopathy (HCM) patients

Procedure: RNS and RDN

DCM

OTHER

dilated non-ischemic cardiomyopathy (DCM) patients

Procedure: RNS and RDN

ICM

OTHER

ischemic cardiomyopathy (ICM) patients

Procedure: RNS and RDN

Interventions

RNS and RDN PROCEDURE

The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation

ARVC; CPVT; DCM; HCM; ICM; long QT syndrome

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient is willing and able to comply with the protocol and has provided written informed consent.
• The patient falls within the target group as stated in 4.1.
• Patient is an acceptable candidate for RDN treatment
• Patient is 18-85 years of age
• Documentation of ventricular arrhythmia (ECG, rhythm strip or ICD interrogation)

You may not qualify if:

• Contraindication to anticoagulation therapy or heparin.
• Previous selective cardiac sympathetic denervation or previous RDN procedure.
• Acute coronary syndrome, cardiac surgery, PCI or stroke within 3 months prior to enrolment.
• Untreated hypothyroidism or hyperthyroidism.
• More than grade 1/3 valvular regurgitation and/or significant valve stenosis (moderate or severe).
• Severe LV dysfunction (LVEF \<20% and/or grade 3/4 diastolic dysfunction).
• Enrolment in another investigational drug or device study.
• Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertile age.
• Mental or physical inability to participate in the study.
• Planned cardiovascular intervention.
• Life expectancy ≤ 12 months.
• Renal artery stenosis \>50% of the arterial lumen, or renal artery lumen ≤3 mm.
• Complex renal artery

Sponsors & Collaborators

• Diagram B.V.: lead

Study Sites (1)

A. Elvan

Zwolle, Overijssel, 8025AB, Netherlands

Location

MeSH Terms

Conditions

Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arif Elvan, MD, PhD

  Isala, department of Cardiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: August 4, 2016
• Study Start: March 3, 2015
• Primary Completion: May 4, 2020
• Study Completion: May 4, 2020
• Last Updated: May 6, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)